Abstract
Exposed collagen surface on diseased blood vessel wall is a trigger of platelet adhesion and subsequent thrombus formation, which is associated with many serious diseases such as myocardial infarction and stroke. Various antithrombotic agents have been developed, but are usually targeted on blood components such as platelet, which suffered from the risk of bleeding due to interference with hemostasis. In contrast, blocking the exposed collagen surface would prevent thrombus formation without the risk of bleeding. In the present study, an antithrombotic nanoconjugate (LWWNSYY-poly glutamic acid, L7-PGA) targeting collagen surface was designed by immobilizing heptapeptide LWWNSYY, a biomimetic inhibitor designed in our previous work, on poly(l-glutamic acid). Successful binding of L7-PGA on the collagen surface was confirmed by a negative ΔG of -5.99 ± 0.26 kcal/mol. L7-PGA was found to effectively inhibit platelet adhesion on the collagen surface, with a reduced IC50 of only 1/5 of that of free LWWNSYY. The inhibition of thrombus formation by L7-PGA was also validated in vivo by a reduction of 31.2% in the weight of thrombus. These results highlight L7-PGA as an effective inhibitor of arterial thrombus formation via blocking exposed collagen surface, which would be helpful for the development of novel antithrombotic nanomedicine.
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More From: Langmuir : the ACS journal of surfaces and colloids
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